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CHICAGO — Tumor debulking does not improve survival in multiorgan metastatic colorectal cancer (CRC), according to a phase 3 trial presented at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.

The trial findings revealed that adding tumor debulking to standard first-line palliative systemic therapy failed to boost progression-free or overall survival across nearly 400 patients with multiorgan disease.

"You'd like to think that there may be some small fraction of patients" helped by the approach, but "the data that we just saw argue" against that assumption, lead investigator Elske Gootjes, MD, PhD, a medical oncologist at Radboud University Medical Center, Nijmegen, Netherlands, concluded when she presented the results of the ORCHESTRA trial.

The use of tumor debulking to treat metastases for multiorgan metastatic CRC has been based on retrospective series that suggest a benefit as well as the emergence of less invasive options, such as thermal ablation and stereotactic radiation, Gootjes explained.

However, until now, no randomized trials have compared the approach against systemic therapy alone.

"We needed [this] trial, we needed prospective data," said Major Kenneth Lee, MD, PhD, a gastrointestinal surgeon at the University of Pennsylvania, Philadelphia, who was the study discussant.

The 382 patients in the ORCHESTRA trial, which ran from 2013 to 2023 in 28 Dutch hospitals, had metastases in at least two organs, with the most common sites being the liver, lung, and peritoneum. About 40% had oligometastatic disease, with fewer than five metastases.

Patients experienced a clinical benefit after three cycles of capecitabine or four cycles of 5-fluorouracil/leucovorin, with many also receiving bevacizumab. These patients were then randomized to either tumor debulking followed by additional systemic therapy (n = 190) or additional systemic therapy alone (n = 192).

Baseline characteristics were well balanced between the groups. About 30% of patients had right-sided primaries, more than half had a RAS or BRAF mutation, and the number of patients with baseline lactate dehydrogenase above 250 U/L and baseline carcinoembryonic antigen above 200 ng/mL was essentially equal between the groups.

Overall, 186 patients went on to continue systemic therapy in the standard group and 162 underwent local treatment in the intervention group, 137 of whom had at least 80% of their tumors removed, the majority by surgery alone or with stereotactic radiation.

Over a median follow-up of 32.3 months, median overall survival was 30 months with debulking vs 27.5 months without it (adjusted hazard ratio, 0.88; P = .23). Median progression-free survival was essentially the same in both the groups — 10.5 months in the debulking arm vs 10.4 months in the standard therapy arm.

In subgroup analyses, the authors found no survival differences in patients with liver and lung metastases only, peritoneal metastases, or durable responses to systemic therapy.

However, 25% of those in the debulking group (41 of 162 patients) ended up with surgical complications of at least a Clavien-Dindo score of 3b, requiring intervention under general anesthesia. Overall, 18 of those in the debulking group (11%) had emergency readmissions, and 6 (4%) died within 90 days.

A lot of us thought that debulking had a beneficial effect, but "these are the data," Gootjes said. There is still a role for debulking to treat symptoms but "not because your patient will live longer."

The trial was funded by the Dutch Colorectal Cancer Group and others. Gootjes and Lee didn't have any disclosures.

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Email: aotto@mdedge.com.